The objective of the Mouse Genetics Core is to establish and manage a resource that will generate and provide mouse models for the studies of cystic fibrosis under this NIH SCOR Program Grant. Specifically, and as described in detail in the individual proposals and below, the new mouse lines to be generated under his Core include: Project 1 (K.L. Kirk)....(Tg) FABP-p11 (WT) and (Tg) FABP-p11 (Mutant) Project 2 (D.J. Benos).....(Tg) CLCA3 and (KO) CLCA3 Project 3 (D.M. Bedwell).... (KI) CFTR-G542 (UGA), (KI) CFTR-G542 (UAG) and (KI) CFTR-G542 UAA). The mouse lines will be generated by oocyte microinjection (Tg) FABP-p1 1 (WT), (Tg) FABP-p1 1 (Mutant) and (Tg) CLCA3) and by embryonic stem cell gene targeting (KO) CLCA3, (KI) CFTR-G542 (UGA), (KI) CFTR-G542 (UAG) and (KI) CFTR-G542 (UAA) technologies, as described in the Research Plan. Confirmation of fidelity to he genomic integration or modification, and the desired expression will be performed under the auspices of the 'individual projects. The Mouse Genetics Core will also establish breeding colonies of the mice described by the individual projects of this NIH SCOR Program, genotype and provide them to the investigators as needed. In addition to generating and propagating the new mouse lines described above, the Mouse Genetics Core will maintain colonies and provide to investigators several established mouse lines relevant to the outlined studies. As described in detail in the individual projects and summarized in the Research Plan, the mouse lines to be maintained under this Core.